The orderly compaction of DNA in nucleosomes along the chromatin fiber is punctuated by highly nuclease-sensitive sites. We found such hypersensitive sites in cellular chromatin by mild cleavage of chromatin in isolated nuclei with DNaseI, and Southern analysis of the partially cut DNA using cloned hybridization probes. We showed that the DNase I hypersensitivity is located at the 5' terminus of several heat-inducible (heat shock) genes in Drosophila, and is present during and before induction. Currently we are trying to probe the fine structure of the DNase I hypersensitive site using DNase I and restriction endonuclease digestion of chromatin, and using high resolution Southern blots to analyze the cleavage patterns. We suggest that preferentially accessible sites in chromatin such as these define a state of potential activity for eukaryotic genes, and may function as entry sites to the DNA sequence for RNA polymerase and control factors.